No abstract

Background Diet‐induced obesity (DIO) and psychological stress are significant independent regulators of gastrointestinal physiology; however, our understanding of how these two disorders influence the host‐microbe interface is still poorly characterized. The aim of this study was to assess the combined influences of diet‐induced obesity and psychological stress on microbiome composition and colonic gene expression. Methods C57BL/6J mice (n = 48) were subject to a combination of 22 weeks of Western diet (WD) feeding and a chronic restraint stressor (CRS) for the last 4 weeks of feeding. At the end of the combined intervention, microbiome composition was determined from cecal contents, and colonic tissue gene expression was assessed by multiplex analysis using NanoString nCounter System and real‐time qPCR. Results WD feeding induced a DIO phenotype with increased body weight, worsened metabolic markers, and alterations to microbiome composition. CRS reduced body weight in both dietary groups while having differential effects on glucose metabolism. CRS improved the Firmicutes/Bacteroidetes ratio in WD‐fed animals while expanding the Proteobacteria phyla. Significantly lower expression of colonic Tlr4 (p = 0.008), Ocln (p = 0.004), and Cldn3 (p = 0.004) were noted in WD‐fed animals compared to controls with no synergistic effects observed when combined with CRS. No changes to colonic expression of downstream inflammatory mediators were observed. Interestingly, higher levels of expression of Cldn2 (p = 0.04) and bile acid receptor Nr1h4 (p = 0.02) were seen in mice exposed to CRS. Conclusion Differential but not synergistic effects of WD and CRS were noted at the host‐microbe interface suggesting multifactorial responses that require further investigation.

Objective Despite the move to at-home, small-volume collection kits to facilitate large population-based studies of faecal microbial compositional profiling, there remains limited reporting on potential impacts of faecal subsampling approaches on compositional profiles. This study aimed to compare the microbial composition from faecal subsamples (< 5 g) collected from the beginning and end of a single bowel movement in ten otherwise healthy adults (6 female, 4 male; age: 24–55 years). Microbial composition was determined by V3–V4 16s rRNA sequencing and compared between subsamples. Results There were no significant differences in OTU count (p = 0.32) or Shannon diversity index (p = 0.29) between the subsamples. Comparison of relative abundance for identified taxa revealed very few differences between subsamples. At the lower levels of taxonomic classification differences in abundance of the Bacillales (p = 0.02) and the Eubacteriaceae family (p = 0.03), and the Eubacterium genera (p = 0.03) were noted. The observation of consistent microbial compositional profiles between faecal subsamples from the beginning and end of a single bowel movement is an important outcome for study designs employing this approach to faecal sample collection. These findings provide assurance that use of a faecal subsample for microbial composition profiling is generally representative of the gut luminal contents more broadly.

Although both diet‐induced obesity and psychological stress are recognized as significant independent contributors to cardiometabolic and behavioral disorders, our understanding of how these two disorders interact and influence cardiometabolic risk and myocardial ischemic tolerance is limited. The aim of this study was to assess the combined effects of an obesogenic diet and psychological stress on cardiometabolic risk factors (body weight, dyslipidemia, insulin sensitivity) and postischemic cardiovascular outcomes. C57Bl/6J mice (n = 48) were subject to a combination of 22 weeks of western diet (WD) feeding and chronic restraint stress (CRS) for the last 4 weeks. Metabolic and behavioral changes were assessed using glucose tolerance tests and open field tests (OFTs), respectively. After 22 weeks, cardiac function and ischemic tolerance were assessed in Langendorff perfused hearts. WD feeding increased body weight and worsened blood lipids and insulin sensitivity. WD‐fed mice also exhibited reduced exploratory behavior within the OFT. CRS reduced body weight and increased locomotion in both dietary groups and had differential effects on fasting glucose metabolism in the two dietary groups while not impacting non‐fasting insulin. Although the WD only marginally reduced reperfusion left ventricular developed pressure recovery, CRS worsened reperfusion diastolic dysfunction in both dietary groups. Interestingly, despite WD+CRS animals exhibiting improved cardiometabolic parameters compared to the WD group, these changes did not translate to marked improvements to postischemic cardiac outcomes. In conclusion, in this study, combined WD feeding and CRS did not act synergistically to worsen cardiometabolic risk factors but instead improved them. Despite these cardiometabolic improvements, WD+CRS increased reperfusion end diastolic pressure which may be indicative of worsened ischemia/reperfusion injury.